Abstract

The purpose of this study is to investigate the therapeutic efficacy of individual or combined doses of dehydro-epiandrosterone (DHEA) and quercetin in ameliorating some biochemical indices in liver of CuO-NPs intoxicated-rats. CuO-NPs (50 nm) was administered as a daily oral dose 100 mg/kg for 2 weeks to rats followed by the fore-mentioned antioxidants for 1 month. We highlighted the therapeutic effect of DHEA and quercetin against CuO-NPs toxicity through monitoring the alteration of liver enzyme activity, antioxidant defense mechanism, necrosis, apoptosis, histopathological alterations, and DNA damage. The rats given CuO-NPs only showed marked significant elevation in liver enzymes, alteration in oxidant-antioxidant balance and an elevation in the hepatic inflammatory marker; tumor necrosis factor-α. Additionally, over expression of both caspase-3 and Bax proteins were detected. Whereas, Bcl2 was down regulated and DNA fragmentation was elevated. Moreover, Histopathological examination of hepatic tissue reinforced the previous biochemical results. Co-treatment with either DHEA, quercetin alone or in combination ameliorated the deviated parameters with variable degrees against CuO-NPs toxicity in rat. In conclusion, our findings suggested that the aforementioned treatments exert therapeutic effect in CuO-NPs toxicity by diminishing oxidative stress, mRNA gene expression and hepatic tissues DNA damage.

Highlights

  • The purpose of this study is to investigate the therapeutic efficacy of individual or combined doses of dehydro-epiandrosterone (DHEA) and quercetin in ameliorating some biochemical indices in liver of CuO-NPs intoxicated-rats

  • Co-administration of either (DHEA) or quercetin (Q) had significantly increased serum total protein level (P < 0.05) and lower serum ALT, AST and bilirubin levels compared with CuO-NPs induced hepatotoxicity group (P < 0.05)

  • Our study revealed that treatment of CuO-NPs intoxicated rats with DHEA and quercetin either alone or in combination alleviate CuO-NPs induced DNA damage which was proved by the decrease of comet length and tail moment

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Summary

Introduction

The purpose of this study is to investigate the therapeutic efficacy of individual or combined doses of dehydro-epiandrosterone (DHEA) and quercetin in ameliorating some biochemical indices in liver of CuO-NPs intoxicated-rats. We highlighted the therapeutic effect of DHEA and quercetin against CuO-NPs toxicity through monitoring the alteration of liver enzyme activity, antioxidant defense mechanism, necrosis, apoptosis, histopathological alterations, and DNA damage. Our findings suggested that the aforementioned treatments exert therapeutic effect in CuO-NPs toxicity by diminishing oxidative stress, mRNA gene expression and hepatic tissues DNA damage. Copper oxide nanoparticles (CuO-NPs) were among the first engineered nanoparticles, due to their exclusive properties and essential applications in magnetic, thermal, electrical and sensor devices as well as cosmetics. Biodistribution experiments revealed that liver, kidney and spleen are the target organs for engineered nanoparticles after uptake by the gastrointestinal t­ract[3] Due to their minute size and surface properties, metal oxide NPs may cross biological barriers and accumulate in different o­ rgans[4]. Apoptotic stimuli leading to destabilization of the mitochondrial integrity precedes activation of caspases which play a central role in the execution of a­ poptosis[10]

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